Among inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease are of unknown cause, and are intractable. Factors associated with inflammatory bowel diseases are abnormalities in the intestinal bacterial flora, secretory IgA production disorder of intestinal epithelial cells, cytokines in the intestinal mucosa, and like factors. The primary lesion of ulcerative colitis is nonspecific chronic inflammation in the large intestine mucosa. Because various autoantibodies are observed therein, ulcerative colitis is considered to have characteristics as an autoimmune disease. On the other hand, Crohn's disease is pathologically characterized by noncaseating granulomatous inflammatory lesions, and dysfunction of monocyte/macrophage cells is considered to be one of the causative factors for the disease. In Japan, the number of ulcerative colitis patients and Crohn's disease patients has steadily increased by slightly less than 10 percent per year, which is problematic.
IBD used to be considered an autoimmune disease. However, with recent advances in research, the inflammation has now been deemed to be caused by intestinal bacteria. It has been reported that intestinal mucosa of IBD patients is less protective against endogenous microflora than in controls, which results in an increase of bacteria in the lumen (see Gastroenterology, 1999, 117: 1089-1097). The use of probiotics as a therapy has been the focus of attention since probiotics were reported to have an effect of preventing and alleviating enteritis. There have been many reports on the treatment of IBD with probiotics (Non-patent Literature (NPL) 1).
Lactic acid bacteria, ingested in the form of fermented milk or the like, are known to exhibit various physiological effects based on their functionality, such as regulation of intestinal functions and reduction of serum cholesterol. As physiological effects of lactic acid bacteria, effects on autoimmune diseases such as chronic rheumatoid arthritis and insulin-dependent diabetes, and inflammatory bowel diseases such as irritable bowel syndrome, ulcerative colitis, and Crohn's disease, have begun to receive attention.
Patent Literature (PTL) 1 discloses that cell debris obtained by crushing bacterial cells of one or more species of lactic acid bacteria selected from the group consisting of lactic acid bacteria belonging to the genera Lactobacillus, Lactococcus, and Streptococcus, has interleukin-10 and interleukin-12 production regulating ability, and the application of this product to Crohn's disease and refractory inflammatory bowel diseases is disclosed.
Patent Literature (PTL) 2 discloses that lactic acid bacteria belonging to Lactobacillus salivarius, which are highly adhesive to mucous membranes and have high proliferation ability and high resistance to acids, are applicable to prevention and/or treatment of ulcerative colitis and Crohn's disease.
Non-patent Literature (NPL) 2 presents experimental results which show that Lactobacillus casei strain GG has the potential to increase the gut IgA immune response and thereby to promote the gut immunological barrier, and reports that Lactobacillus GG could provide an adjunct nutritional therapy for Crohn's disease.
Non-patent Literature (NPL) 3 reports research results which show that Lactobacillus GG may improve gut barrier function and clinical status in children with Crohn's disease.
Non-patent Literature (NPL) 4 reports that intranasal administration of Lactobacillus rhamnosus GG protects mice from influenza virus infection by enhancing respiratory cell-mediated immune responses.
There is also a report that IFN-γ and IL-2 mRNA levels in the mucosa of patients with Crohn's disease are significantly increased, compared to controls, and that chronic intestinal inflammation in patients with Crohn's disease is characterized by an increase of Th1-like cytokines (Non-patent Literature (NPL) 5).
Non-patent Literature (NPL) 6 reports that Lactobacillus kunkeei, which is a new species belonging to the genus Lactobacillus, was isolated from wine. Further, Non-patent Literature (NPL) 7 reports that a fructophilic lactic acid bacteria strain was isolated from a fructose-rich site (flowers), and that the strain was found to contain Lactobacillus kunkeei. Patent Literature (PTL) 3 reports that Lactobacillus kunkeei was isolated from honeybees.